Two-phase study of hepatic artery vascular occlusion with microencapsulated cisplatin in patients with liver metastases from neuroendocrine tumors.
OBJECTIVE
We conducted a two-phase trial in which 100-micron polylactic acid microcapsules with a cisplatin payload (manufactured at our institution [the M. D. Anderson Cancer Center]) were used for hepatic artery occlusion therapy for symptomatic patients who had liver metastases from neuroendocrine tumors.


METHODS
Between January 1993 and December 1995, 20 patients with advanced, unresectable, symptomatic neuroendocrine tumors with liver metastases received repeated hepatic artery occlusion therapy using encapsulated cisplatin. The dose of encapsulated cisplatin was increased in a stepwise fashion. Selective angiography was used to occlude the portion of the hepatic vasculature that had the most metastases with encapsulated cisplatin microcapsules. In each patient, hepatic artery occlusion therapy was repeated in 6-8 weeks and responses were evaluated. Subsequent vascular occlusions were performed on the basis of the level of palliation achieved and the persistence of symptoms.


RESULTS
Of the 20 patients, 17 patients had carcinoid tumors and three had islet cell tumors. The median percentage of liver replacement was approximately 50%. Fifteen of the 20 patients had received prior therapy and 17 patients had hormonal syndrome at the beginning of therapy. One patient had tumor bulk-related symptoms. Nineteen patients had elevated peptides markers that could be followed serially Six patients received encapsulated cisplatin at 50 mg/m2, four patients at 75 mg/m2, and 10 patients at 100 mg/m2 of body surface area. The median number of vascular occlusive procedures per patient was three. All patients were assessable for toxicity and 18 were assessable for response (the other two patients were not assessable because of loss of follow-up). The median follow-up time was 14 months. Twelve (67%) of 18 patients had a median reduction in symptoms of 50%. Eleven (73%) of 15 patients with elevated 24-hr-urine levels of 5-hydroxyindoleacetic acid had a median reduction of 64% for this symptom. We observed objective reduction in the tumors of 14 of the 18 patients. In six of the 14 patients, we noted a partial response. In eight, we observed a minor response. In four of the 18 patients, we noted no response. One treatment-related death resulted from hepatorenal syndrome. Other major complications included hepatic pain (100%), fever (100%), nausea (100%), and vomiting (95%). Also all patients had a transient elevation of liver enzymes. Five of the 20 patients died of disease during our study.


CONCLUSIONS
Hepatic artery vascular occlusion therapy using encapsulated cisplatin is feasible, can palliate symptoms, and can produce biochemical and objective responses in liver metastases from neuroendocrine tumors. The maximum tolerated dose appears to be 100 mg/m2 of body surface area per treatment. Polylactic acid capsules have potential because they can incorporate multiple agents. With surface coating, such capsules can also be used to target specific receptors.
Diamandidou
E
E
Department of Gastroenterology Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Ajani
J A
JA
Yang
D J
DJ
Chuang
V P
VP
Brown
C A
CA
Carrasco
H C
HC
Lawrence
D D
DD
Wallace
S
S
D007516:Adenoma, Islet Cell / Q000628:therapy*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002214:Capsules; D002276:Carcinoid Tumor / Q000556:secondary* / Q000628:therapy*; D016461:Chemoembolization, Therapeutic; D002945:Cisplatin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006499:Hepatic Artery; D006801:Humans; D019344:Lactic Acid; D008113:Liver Neoplasms / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000473:pathology; D010166:Palliative Care / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000473:pathology; D011091:Polyesters; D011108:Polymers; D013997:Time Factors
D000970:Antineoplastic Agents; D002214:Capsules; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D002945:Cisplatin